The protozoan parasite Plasmodium is the causative agent of malaria, which remains one of the most prominent public health challenges in the world today. The overall goal of this project is to examine and define the potential protective roles of interleukin (IL)-17 during an immune response against Plasmodium. Our preliminary studies using IL-17RA-deficient mice indicate that these mice are susceptible to Plasmodium yoelii 17X infection, characterized by a rapid increase in parasite burden, earlier onset of anemia, deficiency in IL-12 and IFN-?? production, and death during the acute stage of the infection, although P. yoelii 17X infection is non-lethal in wild-type mice. Additionally, surfaces of splenic dendritic cells isolated from IL-17RA-deficient mice expressed reduced amounts of major histocompatibility class II molecules than dendritic cells from wild-type mice. Based on these findings, we hypothesize that the absence of IL-17 signaling results in impaired dendritic cell function and an inability to mount a protective immune response to control this infection. We propose to (Aim 1) determine whether the absence of IL-17 alters dendritic cell phenotype after P. yoelii 17X infection in order to identify the extent to which dendritic cells contribute to the observed phenotype. Additionally, we propose to (Aim 2) determine whether IL-17RA-deficient mice can be rescued from their lethal phenotype. Results obtained from the proposed experiments will define the roles of IL-17 in enhancing a protective TH1 response after Plasmodium infection, offering new strategies to enhance protective immunity as part of anti-malarial vaccines by creating vaccine formulations that are able to induce IL-17 as a means of inducing a stronger parasite-specific TH1 response. PUBLIC HEALTH RELEVANCE: Malaria causes an enormous medical, economical and emotional burden throughout the world. Thus, an emphasis has been placed on understanding how the immune response, both cell and antibody-mediated, regulates the outcome of this infection in order to determine how protective immunity can be enhanced in a vaccine setting to ultimately provide and maintain immunity against this disease.